Transforming growth factor-β1expression in early biopsy specimen predicts long-term graft function following pediatric renal transplantation

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Abstract
The main cause of late graft loss or declining long‐term graft function is chronic allograft nephropathy (CAN), characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)‐β1 plays a key role in fibrogenesis. We immunohistochemically investigated whether the degree of TGF‐β1 expression in early biopsy specimens routinely obtained from stable allografts at 100 d could predict fibrosis and graft dysfunction in the late phase. Patients were children with grafts from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF‐β1 in the graft using LC antibody (LC) for intracellular TGF‐β1 and CC antibody (CC) for extracellular TGF‐β1. The change in creatinine clearance between 100 d and 3 yr after transplantation (ΔCcr) was used as an index of long‐term graft function. We also used image analysis to calculate the relative area involved by interstitial fibrosis in the trichrome‐stained section of graft biopsy specimens at 100 d and 3 yr, designating the change as ΔFI. ΔCcr was −4.2±9.4 mL/min in subjects with minimal early immunoreactivity for CC and −20.5±15.9 mL/min in subjects with strong reactivity (p1 expression in grafts at 100 d after transplantation is associated with a long‐term decline in graft function and tends to be associated with increased graft fibrosis at 3 yr.